The present invention relates to a process for producing a solid dispersion of an active ingredient which comprises feeding the active ingredient and a matrix-forming agent to an extruder and forming a uniform extrudate.
A continuous process for producing solid pharmaceutical forms, including solid solution products, has been known for some time and entails converting a melt of polymeric binder which contains active ingredients into the required drug form by injection molding or extrusion and subsequent shaping (see, for example, EP-A-240 904, EP-A-240 906 and EP-A-337 256). Satisfactory results are obtained in this process when the active ingredient has a low melting point and/or a high solubility in the molten polymeric binder. Active ingredients having a low melting point are liquefied upon contact with the polymeric binder melt, and the liquefied active ingredient can be readily dispersed in the polymeric binder melt. Alternatively, active ingredients having a high solubility in the molten polymeric binder readily dissolve in the polymeric binder melt.
Problems occur when the active ingredient has a high melting point and/or a limited solubility in the molten polymeric binder. Adequate dispersion of the active ingredient may require high temperatures of the extruder barrel, a relatively long mixing time and/or high shear in order to bring about sufficient mixing of the active ingredient with the polymeric binder melt. This may result in local overheating and damage to the product, especially when a shear- and temperature-sensitive active ingredient is being used. A further disadvantage of the necessity of high temperatures of the extruder barrel is high energy costs.
Furthermore, EP 0 580 860 B2 describes a process for producing a solid dispersion of a drug dissolved in a polymer, wherein a twin-screw extruder equipped with paddle means or kneading blocks is employed. Such kneading blocks consist of, e.g. disk cams disposed offset in the manner of a spiral staircase. The substance is pressed through a narrow tapered gap between the disk cams and the extruder housing. During the passage through the extruder, the material is thus subjected to high local shear forces, which may lead to excessive degradation of the active ingredient and/or the polymer. Shearing may also cause excessive wear of the extrusion equipment.